Aerosol-Assisted Synthesis of Tailor-Made Hollow Mesoporous Silica Microspheres for Controlled Release of Antibacterial and Anticancer Agents.
Aerosol-Assisted Synthesis of Tailor-Made Hollow Mesoporous Silica Microspheres for Controlled Release of Antibacterial and Anticancer Agents.
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DOI：
10.1021/acsami.9b20510
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发表时间：
2020-01
影响因子：
9.5
通讯作者：
Jalal Poostforooshan;S. Belbekhouche;M. Shaban;Vanessa Alphonse;Damien Habert;N. Bousserrhine;J. Courty;A. Weber
中科院分区：
文献类型：
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作者：
Jalal Poostforooshan;S. Belbekhouche;M. Shaban;Vanessa Alphonse;Damien Habert;N. Bousserrhine;J. Courty;A. Weber
中空介孔二氧化硅微球(HMSM)以其巨大的中空载药内腔和可渗透的介孔壳层用于药物控制释放，是最有前途的药物载体之一。在这里，我们报告了一种易于控制的气溶胶为基础的方法，通过连续喷雾干燥胶体二氧化硅纳米颗粒和Eudradit/Triton X100复合纳米球(EUT)作为模板，然后移除模板。重要的是，通过调节实验条件(即二氧化硅与纳米二氧化硅的质量比和粒径)，可以在一定程度上调节中空腔的内部结构和介孔壳层的外部形貌和孔隙率，以优化载药能力和控释性能。然后，通过将阿莫西林作为一种包封率高达46%的抗生素化合物，考察了气雾化合成的HMSM微粒在药物控释中的应用。此外，为了提高阿莫西林负载的HMSM颗粒的生物相容性，通过逐层组装的方法对其表面进行了聚烯丙胺和海藻酸盐的功能化处理。所得颗粒对大肠杆菌(革兰氏阴性)细菌的抑制率在不到2小时内达到90%。最后，我们探索了HMSM作为胰腺癌药物载体的多功能性。针对胰腺肿瘤细胞外介质的pH值低于正常组织的特点，将pH敏感的壳聚糖接枝到HMSM表面，然后负载促凋亡的NCL拮抗剂(N6L)作为抗癌药物。所得微粒具有pH响应性的药物释放和良好的抗癌活性，对癌细胞生长的抑制率高达60%。
Hollow mesoporous silica microsphere (HMSM) particles are one of the most promising vehicles for efficient drug delivery owing to their large hollow interior cavity for drug loading and the permeable mesoporous shell for controlled drug release. Here we report an easily controllable aerosol-based approach to produce HMSM particles by continuous spray-drying of colloidal silica nanoparticles and Eudragit/Triton X100 composite (EUT) nanospheres as templates, followed by templates removal. Importantly, the internal structure of the hollow cavity and the external morphology and the porosity of the mesoporous shell can be tuned to a certain extent by adjusting the experimental conditions (i.e., silica to EUT mass ratio and particle size of silica nanoparticles) to optimize the drug loading capacity and the controlled-release properties. Then, the application of aerosol-synthesized HMSM particles in controlled drug delivery was investigated by loading amoxicillin as an antibiotic compound with high entrapment efficiency (up to 46%). Furthermore, to improve the biocompatibility of the amoxicillin-loaded HMSM particles, their surfaces were functionalized with poly(allylamine) and alginate as biocompatible polymers via the layer-by-layer (LbL) assembly. The resulting particles were evaluated towards Escherichia coli (Gram-negative) bacteria and indicated the bacterial inhibition up to 90% in less than 2 hours. Finally, we explored the versatility of HMSMs as drug carriers for pancreatic cancer treatment. Because the pH value of the extracellular medium in pancreatic tumors is lower than that of healthy tissue, chitosan as a pH-sensitive gatekeeper was grafted to the HMSM surface and then loaded with a pro-apoptotic NCL antagonist agent (N6L) as an anticancer drug. The obtained particles exhibited pH-responsive drug releases and excellent anticancer activities with inhibition of cancer cell growth up to 60%.